Use of a linear b cell epitope of ns1 protein to treat dengue virus

Abstract

Disclosed herein are isolated flavivirus polypeptides comprising an amino acid sequence at least 75% identical to one of SEQ ID NOs: 1-11, or a nucleic acid encoding the polypeptide, or a viral like particle encoding the polypeptide, wherein the polypeptide does not comprise the amino acid sequence of a full-length flavivirus NS1 polypeptide. Methods of using these polypeptides are also disclosed, such as for preventing, treating, or determining the prognosis of a flavivirus infection.

1 . An isolated polypeptide comprising an amino acid sequence at least 75% identical to one of SEQ ID NOs: 1-11, or a nucleic acid molecule encoding the polypeptide, or an isolated viral like particle comprising the polypeptide, wherein the polypeptide is at most 50 amino acids in length and does not comprise the amino acid sequence of a full-length  flavivirus  NS1 polypeptide. 
     
     
         2 . The isolated polypeptide of  claim 1 , wherein the polypeptide is at most 20 amino acids in length. 
     
     
         3 . The isolated polypeptide of  claim 1 , wherein the polypeptide comprises the amino acid sequence of one of SEQ ID NOs: 9-11. 
     
     
         4 . The isolated polypeptide of  claim 3 , wherein the polypeptide consists of one of SEQ ID NOs: 9-11. 
     
     
         5 . The isolated polypeptide of  claim 1 , wherein the polypeptide comprises an amino acid sequence at least 75% identical to one of SEQ ID NOs: 1-8. 
     
     
         6 . The isolated polypeptide of  claim 5 , wherein the polypeptide comprises the amino acid sequence of one of SEQ ID NOs: 1-8. 
     
     
         7 . The isolated polypeptide of  claim 6 , wherein the polypeptide consists of the amino acid sequence of one of SEQ ID NOs: 1-8. 
     
     
         8 . A recombinant nucleic acid molecule comprising a heterologous promoter operably linked to a nucleic acid molecule encoding the polypeptide of  claim 1 . 
     
     
         9 . A vector comprising the nucleic acid molecule of  claim 8 . 
     
     
         10 . The isolated virus-like particle (VLP) of  claim 1 . 
     
     
         11 . The isolated virus-like particle of  claim 8 , wherein the polypeptide consists of the amino acid sequence of one of SEQ ID NOs: 1-11. 
     
     
         12 . An immunogenic composition comprising the polypeptide, the nucleic acid molecule, or the viral like particle of  claim 1 , and a pharmaceutically acceptable carrier. 
     
     
         13 . The immunogenic composition of  claim 12 , further comprising an adjuvant. 
     
     
         14 . A method for inducing an immune response to a  flavivirus , comprising administering to the subject an effective amount of the immunogenic composition of  claim 12 , thereby inducing an immune response to a  flavivirus.    
     
     
         15 . The method of  claim 14 , wherein the subject has a  flavivirus  virus infection. 
     
     
         16 . The method of  claim 15 , wherein the  flavivirus  is a dengue virus. 
     
     
         17 . The method of  claim 14 , wherein the subject is healthy, and the method prevents an infection with the  flavivirus  or reduces the severity of a future  flavivirus  infection. 
     
     
         18 . The method of  claim 17 , wherein the  flavivirus  is a dengue virus. 
     
     
         19 . The method of  claim 18 , wherein the method prevents, or reduces the severity of, dengue virus hemorrhagic fever. 
     
     
         20 . (canceled) 
     
     
         21 . The method of  claim 14 , wherein the subject is human. 
     
     
         22 . The method of  claim 14 , comprising a prime boost administration of the immunogenic composition. 
     
     
         23 . A method for determining the effectiveness of a therapeutic agent for the treatment of a  flavivirus  infection in a subject, comprising
 contacting a biological sample comprising antibodies from the subject treated with the therapeutic agent with a polypeptide consisting of one of SEQ ID NO: 1-11, under conditions sufficient to form an immune complex;   measuring the immune complex; and   wherein detection of the immune complex determines that the agent is effective for treating the subject.   
     
     
         24 - 25 . (canceled) 
     
     
         26 . A method for determining the prognosis of a  flavivirus  infection in a subject, comprising
 contacting a biological sample comprising antibodies from the subject with a polypeptide consisting of one of SEQ ID NOs: 1-11 to form an immune complex; and   comparing the amount of the immune complex to a control,   wherein an increase in the immune complex as compared to the control indicates a good prognosis for the subject.   
     
     
         27 - 30 . (canceled) 
     
     
         31 . A method of passively immunizing a subject against a  flavivirus , comprising administering to the subject a therapeutically effective amount of an antibody that specifically binds a polypeptide consisting of the amino acid sequence of one of SEQ ID NOs: 1-11, thereby passively immunizing the subject against the  flavivirus.    
     
     
         32 . The method of  claim 11 , wherein the  flavivirus  is a Dengue virus.